Dynamic niches in the origination and differentiation of haematopoietic stem cells

Haematopoietic stem cells (HSCs) are multipotent, self-renewing progenitors that generate all mature blood cells. HSC function is tightly controlled to maintain haematopoietic homeostasis, and this regulation relies on specialized cells and factors that constitute the haematopoietic 'niche', or microenvironment. Recent discoveries, aided in part by technological advances in in vivo imaging, have engendered a new appreciation for the dynamic nature of the niche, identifying novel cellular and acellular niche components and uncovering fluctuations in the relative importance of these components over time. These new insights significantly improve our understanding of haematopoiesis and raise fundamental questions about what truly constitutes a stem cell niche.

[1]  L. Calvi,et al.  Communications between bone cells and hematopoietic stem cells. , 2008, Archives of biochemistry and biophysics.

[2]  G. Cossu,et al.  Smooth muscle of the dorsal aorta shares a common clonal origin with skeletal muscle of the myotome , 2006, Development.

[3]  Younghun Jung,et al.  Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. , 2006, Bone.

[4]  G. Yarrington.  Molecular Cell Biology , 1987, The Yale Journal of Biology and Medicine.

[5]  R. Lemieux,et al.  Increased megakaryopoiesis in cultures of CD34‐enriched cord blood cells maintained at 39°C , 2004 .

[6]  Y. Ko,et al.  Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size , 2005, The Journal of experimental medicine.

[7]  D. Sugiyama,et al.  Cold exposure down-regulates zebrafish hematopoiesis. , 2010, Biochemical and biophysical research communications.

[8]  F. Ducongé,et al.  In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution. , 2008, Blood.

[9]  L. Espinosa,et al.  The Notch pathway in the developing hematopoietic system. , 2010, The International journal of developmental biology.

[10]  Linheng Li,et al.  Cadherin-based adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow. , 2010, Cell stem cell.

[11]  D. Scadden,et al.  Role of the Osteoblast Lineage in the Bone Marrow Hematopoietic Niches , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  L. Zon,et al.  Isolation and characterization of runxa and runxb, zebrafish members of the runt family of transcriptional regulators. , 2002, Experimental hematology.

[13]  Elaine Dzierzak,et al.  Of lineage and legacy: the development of mammalian hematopoietic stem cells , 2008, Nature Immunology.

[14]  A. Ho,et al.  Aging of hematopoietic stem cells is regulated by the stem cell niche , 2008, Experimental Gerontology.

[15]  G. Haan,et al.  Hematopoietic stem cell aging and self-renewal , 2007, Cell and Tissue Research.

[16]  George Q. Daley,et al.  Biomechanical forces promote embryonic haematopoiesis , 2009, Nature.

[17]  Li Sun,et al.  Diet‐induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice , 2010, Annals of the New York Academy of Sciences.

[18]  G. Tonini,et al.  EBNA-negative polyclonal B cells derived from a long-term culture of unclassified acute lymphoblastic leukemia: IL-2-like activity of culture's supernatant. , 1986, International journal of cell cloning.

[19]  J. Abkowitz,et al.  Mobilization as a preparative regimen for hematopoietic stem cell transplantation. , 2004, Blood.

[20]  F. Wolber,et al.  Roles of spleen and liver in development of the murine hematopoietic system. , 2002, Experimental hematology.

[21]  F. Staal,et al.  WNT Proteins: Environmental Factors Regulating HSC Fate in the Niche , 2009, Annals of the New York Academy of Sciences.

[22]  E. Laurenti,et al.  Enhanced c-Met activity promotes G-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling. , 2011, Blood.

[23]  Ben D. MacArthur,et al.  Mesenchymal and haematopoietic stem cells form a unique bone marrow niche , 2010, Nature.

[24]  T. Suda,et al.  Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells. , 2010, Blood.

[25]  Jichun Chen,et al.  Hematopoiesis in 3 dimensions: human and murine bone marrow architecture visualized by confocal microscopy. , 2010, Blood.

[26]  Colleen Delaney,et al.  Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution , 2010, Nature Medicine.

[27]  A. Zannettino,et al.  Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. , 2010, Blood.

[28]  S. Morrison,et al.  Supplemental Experimental Procedures , 2022 .

[29]  R. Taichman,et al.  Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures. , 1996, Blood.

[30]  B. Williams,et al.  Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. , 2005, Blood.

[31]  J. H. Sang,et al.  The Drosophila Ovary , 1970 .

[32]  W. His.  Lecithoblast und Angioblast der Wirbelthiere : histogenetische Studien , 1900 .

[33]  O. Hermine,et al.  Human Bone Marrow Adipocytes Block Granulopoiesis Through Neuropilin‐1‐Induced Granulocyte Colony‐Stimulating Factor Inhibition , 2008, Stem cells.

[34]  D. Lai,et al.  Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression. , 2011, Blood.

[35]  S. Orkin,et al.  The placenta is a niche for hematopoietic stem cells. , 2004, Developmental cell.

[36]  E. Fuchs,et al.  Defining the Epithelial Stem Cell Niche in Skin , 2004, Science.

[37]  Linheng Li,et al.  The stem cell niches in bone. , 2006, The Journal of clinical investigation.

[38]  K. Parmar,et al.  Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia , 2007, Proceedings of the National Academy of Sciences.

[39]  H. Nakauchi,et al.  Age-Associated Characteristics of Murine Hematopoietic Stem Cells , 2000, The Journal of experimental medicine.

[40]  A. Iwama,et al.  Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells , 2006, The EMBO journal.

[41]  Wei Wang,et al.  Proteomic analysis of interstitial fluid in bone marrow identified that peroxiredoxin 2 regulates H(2)O(2) level of bone marrow during aging. , 2010, Journal of proteome research.

[42]  D. Stainier,et al.  Hematopoietic stem cells derive directly from aortic endothelium during development , 2009, Nature.

[43]  Charles P. Lin,et al.  Bone progenitor dysfunction induces myelodysplasia and secondary leukemia , 2010, Nature.

[44]  R. Oostendorp,et al.  Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent supporters of hematopoietic stem cell activity. , 2002, Blood.

[45]  I. Weissman,et al.  Cell intrinsic alterations underlie hematopoietic stem cell aging. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[46]  C. Ackert-Bicknell,et al.  Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. , 2009, Critical reviews in eukaryotic gene expression.

[47]  J. Krosl,et al.  A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations. , 2010, Blood.

[48]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[49]  S. Orkin,et al.  Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment , 2007, Cell.

[50]  C. Magnon,et al.  Trafficking of hematopoietic stem cells during embryogenesis and fetal development , 2008 .

[51]  N. Galjart,et al.  In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium , 2010, Nature.

[52]  P. Chambon,et al.  A Microenvironment-Induced Myeloproliferative Syndrome Caused by Retinoic Acid Receptor γ Deficiency , 2007, Cell.

[53]  D. Scadden,et al.  Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. , 2008, Cell stem cell.

[54]  Winfried Wiegraebe,et al.  Detection of functional haematopoietic stem cell niche using real-time imaging , 2009, Nature.

[55]  N. Shiojiri.  Development and differentiation of bile ducts in the mammalian liver , 1997, Microscopy research and technique.

[56]  D. Scadden,et al.  Osteoblastic cells regulate the haematopoietic stem cell niche , 2003, Nature.

[57]  P. Marks,et al.  Differentiation of normal and neoplastic hematopoietic cells , 1978 .

[58]  P. Frenette,et al.  Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone Marrow , 2006, Cell.

[59]  Younghun Jung,et al.  Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells. , 2007, Blood.

[60]  Gordana Vunjak-Novakovic,et al.  Biomimetic platforms for human stem cell research. , 2011, Cell stem cell.

[61]  Lecithoblast und Angioblast der Wirbelthiere , 1901, Nature.

[62]  C. A. Rosselló,et al.  Gene transfer by electroporation into hemogenic endothelium in the avian embryo , 2010, Developmental dynamics : an official publication of the American Association of Anatomists.

[63]  Irving L. Weissman,et al.  Physiological Migration of Hematopoietic Stem and Progenitor Cells , 2001, Science.

[64]  T. Suda,et al.  Niche Regulation of Hematopoietic Stem Cells in the Endosteum , 2009, Annals of the New York Academy of Sciences.

[65]  R. Bronson,et al.  Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  E. Shpall,et al.  Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells. , 2004, Cytotherapy.

[67]  Yang Liu,et al.  mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells , 2009, Science Signaling.

[68]  N. Fujii,et al.  The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. , 2010, Immunity.

[69]  Elaine Dzierzak,et al.  Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. , 2002, Immunity.

[70]  Zev Rosenwaks,et al.  Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. , 2009, Cell stem cell.

[71]  R. Schofield.  The relationship between the spleen colony-forming cell and the haemopoietic stem cell. , 1978, Blood cells.

[72]  T. Nagasawa,et al.  Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. , 2006, Immunity.

[73]  B. Schmit,et al.  Epidermal Neural Crest Stem Cell (EPI-NCSC)—Mediated Recovery of Sensory Function in a Mouse Model of Spinal Cord Injury , 2010, Stem Cell Reviews and Reports.

[74]  A. Nagler,et al.  Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling , 2007, Nature Immunology.

[75]  C. Cunningham,et al.  Pharmacologic modulation of the calcium-sensing receptor enhances hematopoietic stem cell lodgment in the adult bone marrow. , 2011, Blood.

[76]  P. Frenette,et al.  Hematopoietic Stem Cell Trafficking , 2007, Annals of the New York Academy of Sciences.

[77]  S. Morrison,et al.  Uncertainty in the niches that maintain haematopoietic stem cells , 2008, Nature Reviews Immunology.

[78]  Kathryn E. Crosier,et al.  Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis. , 2002, Development.

[79]  I. Weissman,et al.  Circulation and Chemotaxis of Fetal Hematopoietic Stem Cells , 2004, PLoS biology.

[80]  M. Bredella,et al.  Vertebral Bone Marrow Fat Is Positively Associated With Visceral Fat and Inversely Associated With IGF‐1 in Obese Women , 2011, Obesity.

[81]  Kathryn E. Crosier,et al.  Runx3 is required for hematopoietic development in zebrafish , 2003, Developmental dynamics : an official publication of the American Association of Anatomists.

[82]  S. Rafii,et al.  Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells , 2010, Nature Cell Biology.

[83]  H. Broxmeyer,et al.  The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. , 1991, Cancer cells.

[84]  A. Spradling,et al.  A niche maintaining germ line stem cells in the Drosophila ovary. , 2000, Science.

[85]  S. Nishikawa,et al.  Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 , 1996, Nature.

[86]  H. Qian,et al.  Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells. , 2007, Blood.

[87]  D. Rowe,et al.  Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. , 2004, Blood.

[88]  A. Cumano,et al.  Lymphoid Potential, Probed before Circulation in Mouse, Is Restricted to Caudal Intraembryonic Splanchnopleura , 1996, Cell.

[89]  M. Lichtman.  Obesity and the Risk for a Hematological Malignancy: Leukemia, Lymphoma, or Myeloma , 2010, The oncologist.

[90]  Christie M. Orschell,et al.  Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist , 2005, The Journal of experimental medicine.

[91]  Lina A. Thoren,et al.  Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. , 2007, Cell stem cell.

[92]  E. Brown,et al.  Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor , 2006, Nature.

[93]  J. Till,et al.  The cellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl-Sld. , 1965, Blood.

[94]  S. Thrun,et al.  Substrate Elasticity Regulates Skeletal Muscle Stem Cell Self-Renewal in Culture , 2010, Science.

[95]  David W. Rowe,et al.  Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche , 2009, Nature.

[96]  A. Wagers,et al.  Improved cutaneous healing in diabetic mice exposed to healthy peripheral circulation. , 2009, The Journal of investigative dermatology.

[97]  M. Bhatia,et al.  Analysis of the human fetal liver hematopoietic microenvironment. , 2005, Stem cells and development.

[98]  I. Kaplan,et al.  Early and late bone-marrow changes after irradiation: MR evaluation. , 1990, AJR. American journal of roentgenology.

[99]  L. Zon,et al.  Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration , 2009, Cell.

[100]  K. Kissa,et al.  Blood stem cells emerge from aortic endothelium by a novel type of cell transition , 2010, Nature.

[101]  K. Ottersbach,et al.  The murine placenta contains hematopoietic stem cells within the vascular labyrinth region. , 2005, Developmental cell.

[102]  M. Boulton,et al.  Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock , 2009, The Journal of experimental medicine.

[103]  J. Barker.  Sl/Sld hematopoietic progenitors are deficient in situ. , 1994, Experimental hematology.

[104]  Matthias Gunzer,et al.  Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones. , 2009, Blood.

[105]  Matthias P. Lutolf,et al.  Designing materials to direct stem-cell fate , 2009, Nature.

[106]  P. Conte,et al.  Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation. , 2009, Blood.

[107]  吉原 宏樹.  Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche , 2008 .

[108]  G. Daley,et al.  Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment , 2009, Nature.

[109]  E. Srour,et al.  Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. , 2010, Blood.

[110]  W. Bolch,et al.  Spatial gradients of blood vessels and hematopoietic stem and progenitor cells within the marrow cavities of the human skeleton. , 2009, Blood.

[111]  R. Taichman,et al.  Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. , 2000, The Journal of clinical investigation.

[112]  Albert J. Keung,et al.  Biophysics and dynamics of natural and engineered stem cell microenvironments , 2010, Wiley interdisciplinary reviews. Systems biology and medicine.

[113]  Ari Elson,et al.  Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells , 2006, Nature Medicine.

[114]  Shoham Shivtiel,et al.  Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment. , 2008, Cell stem cell.

[115]  A. Koniski,et al.  Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. , 1999, Developmental biology.

[116]  D. Levy.  NF-kappaB-ISGF3 transcription factor cooperation: coincidence detector or memory chip? , 2010, Immunity.

[117]  Anthony E. Boitano,et al.  Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells , 2010, Science.

[118]  Ian A. White,et al.  Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. , 2010, Cell stem cell.

[119]  J. White,et al.  On the control of germ cell development in Caenorhabditis elegans. , 1981, Developmental biology.

[120]  David A. Williams,et al.  The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS. , 2010, Blood.

[121]  Andrea T. Badillo,et al.  The regulatory role of stromal microenvironments in fetal hematopoietic ontogeny , 2006, Stem Cell Reviews.

[122]  Pernilla Eliasson,et al.  The hematopoietic stem cell niche: Low in oxygen but a nice place to be , 2010, Journal of cellular physiology.

[123]  T. Suda,et al.  Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. , 2010, Blood.

[124]  Keisuke Ito,et al.  Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche , 2004, Cell.

[125]  D. Caramella,et al.  Hematopoietic bone marrow recovery after radiation therapy: MRI evaluation , 1989 .

[126]  Pernilla Eliasson,et al.  Hypoxia mediates low cell-cycle activity and increases the proportion of long-term-reconstituting hematopoietic stem cells during in vitro culture. , 2010, Experimental hematology.

[127]  P. Mangeot,et al.  Expression of Pitx2 in stromal cells is required for normal hematopoiesis. , 2006, Blood.

[128]  C. Meshul,et al.  FNA of extraskeletal myxoid chondrosarcoma: Cytomorphologic, EM, and X‐ray microanalysis features , 1994, Diagnostic cytopathology.

[129]  P. Fraker,et al.  A role for leptin in sustaining lymphopoiesis and myelopoiesis , 2008, Proceedings of the National Academy of Sciences.

[130]  E. Domany,et al.  A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal. , 2010, Cell stem cell.

[131]  N. Horwood,et al.  Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo. , 2011, Blood.

[132]  D. Rowe,et al.  Conditional Ablation of the Osteoblast Lineage in Col2.3Δtk Transgenic Mice , 2001 .

[133]  B. Göttgens,et al.  Ontogeny of haematopoiesis: recent advances and open questions , 2010, British journal of haematology.

[134]  T. Martin,et al.  What is the true nature of the osteoblastic hematopoietic stem cell niche? , 2009, Trends in Endocrinology & Metabolism.

[135]  A. Trumpp,et al.  The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in , 2011, The Journal of experimental medicine.

[136]  Shin-Ichi Nishikawa,et al.  Continuous single-cell imaging of blood generation from haemogenic endothelium , 2009, Nature.

[137]  A. M. Morrison,et al.  Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. , 2002, Development.

[138]  Cheng Cheng Zhang,et al.  The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. , 2010, Cell stem cell.

[139]  Sean J. Morrison,et al.  Stem Cells and Niches: Mechanisms That Promote Stem Cell Maintenance throughout Life , 2008, Cell.

[140]  S. Morrison,et al.  An in vivo model to study and manipulate the hematopoietic stem cell niche. , 2010, Blood.

[141]  L. Calvi,et al.  Notch signaling and the bone marrow hematopoietic stem cell niche. , 2010, Bone.

[142]  P. Murray.  The development in vitro of the blood of the early chick embryo , 1932 .

[143]  K. Ottersbach,et al.  Identification of novel regulators of hematopoietic stem cell development through refinement of stem cell localization and expression profiling. , 2009, Blood.

[144]  K. Yutzey,et al.  Notch signaling and the developing skeleton. , 2012, Advances in experimental medicine and biology.

[145]  S. Nishikawa,et al.  Cell tracing shows the contribution of the yolk sac to adult haematopoiesis , 2007, Nature.

[146]  Ting Xie,et al.  decapentaplegic Is Essential for the Maintenance and Division of Germline Stem Cells in the Drosophila Ovary , 1998, Cell.

[147]  Paul J. Williams,et al.  High fat diet-induced animal model of age-associated obesity and osteoporosis. , 2010, The Journal of nutritional biochemistry.

[148]  R. Marcos,et al.  Formation of micronucleated erythrocytes in mouse bone-marrow under conditions of hypothermia is not associated with stimulation of erythropoiesis. , 2008, Mutation research.

[149]  I. Weissman,et al.  Endochondral ossification is required for hematopoietic stem cell niche formation , 2008, Nature.

[150]  M. Warr,et al.  Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. , 2010, Cell stem cell.

[151]  Haiyang Huang,et al.  Identification of the haematopoietic stem cell niche and control of the niche size , 2003, Nature.

[152]  G. de Haan,et al.  Mouse strain-dependent changes in frequency and proliferation of hematopoietic stem cells during aging: correlation between lifespan and cycling activity. , 1997, Blood.

[153]  W. Goessling,et al.  Previews. NOTCHing an arrow at cord blood: translating stem cell knowledge into clinical practice. , 2010, Cell stem cell.

[154]  G. van Zant,et al.  Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. , 2005, Blood.